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Koochaki R, Nabiuni M, Amini E. In Vitro and In Vivo Effects of Quillaja saponaria Bark Saponin Against Ovarian Cancer Cells. Pharm Biomed Res 2026; 12 (3) :195-206
URL: http://pbr.mazums.ac.ir/article-1-755-en.html

Background: Ovarian cancer is one of the most lethal gynecologic cancers in the world. It has also characterized by late diagnosis, high recurrence rate, and poor  prognosis. The advanced stage at diagnosis and the development of chemoresistance are major challenges in its treatment, leading to limited therapeutic options and decreased survival rates. Natural products have emerged as a promising source of novel anticancer agents due to their diverse bioactive compounds and potential to target multiple signaling pathways involved in cancer initiation and progression.
Objectives: Ovarian cancer metastasis is the leading cause of cancer-related deaths in women worldwide. The effects of Quillaja saponaria bark saponin (QBS) on the viability and epithelial-mesenchymal transition (EMT) potential of human ovarian epithelial SKOV-3 and A2780 cells, and the cytotoxicity effect of QBS in the rat ovarian cancer model have been investigated.
Methods: The cytotoxicity of QBS against SKOV3 and A2780 cells was evaluated using the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to calculate IC50 values. The scratch assay assessed cell migration. To explore molecular changes in metastasis, the expression of key EMT-related genes, including ITGA5, MMP2, Zeb1, and CDH1 was measured by real-time polymerase chain reaction. For the in vivo assay, the 7,12-dimethylbenz[a]anthracene (DMBA)-induced ovarian cancer rat model was used. 
Results: The MTT assay demonstrated that QBS did not exert significant toxicity on NIH3T3 as normal cells; nevertheless, it induced cytotoxicity against A2780 and SKOV3 cells in a dose and time-dependent manner; IC50 was determined as 82 and 77 μg/mL for SKOV3 and A2780 cells, respectively. The scratch assay revealed that QBS significantly attenuated cell invasion at sub-IC50 concentrations (20 and 30 µg/mL). Gene expression indicated down-regulation of Zeb1, ITGA5, and MMP2 at the IC50 value of both SKOV3 and A2780 cells (P≤0.001). Also, up-regulation of CDH1 in A2780 cells at the IC50 value was significant (P≤0.001). The in vivo assay showed that QBS significantly reduced tumor growth (P≤0.01) and protected rats against 7,12- DMBA-induced ovarian cancer, with optimal effect of 16 mg/kg.
Conclusion: Overall, QBS can offer a potent cytotoxic agent against ovarian cancer cells in vitro and in vivo. However, this hypothesis requires further investigation to discover the molecular signaling pathway in human ovarian cancer cells.